Miyaura Cross-coupling Reaction Research Articles

Synthesis and characterization of an isopropylBippyPhos precatalyst

A review of our high throughput reaction screening data revealed that BippyPhos was frequently associated with successful outcomes in Buchwald – Hartwig amination reactions. A barrier to the wider use of this ligand, particularly among those performing smaller scale work, may be the lack of a readily available precatalyst. We describe the multi-gram synthesis and characterization of isopropylBippyPhos, and its conversion to isopropylBippyPhos Pd G2, a biaryl phosphine precatalyst. We demonstrate the competency of isopropylBippyPhos Pd G2 in palladium catalyzed Buchwald – Hartwig amination reactions and in Suzuki – Miyaura cross coupling reactions.

Preparation of Metal-Immobilized Methacrylate-Based Monolithic Columns for Flow-Through Cross-Coupling Reactions.

With the aim of developing efficient flow-through microreactors for high-throughput organic synthesis, in this work, microreactors were fabricated by chemically immobilizing palladium-, nickel-, iron-, and copper-based catalysts onto ligand-modified poly(glycidyl methacrylate-co-ethylene dimethacrylate) [poly(GMA-co-EDMA)] monoliths, which were prepared inside a silicosteel tubing (10 cm long with an inner diameter of 1.0 mm) and modified with several ligands including 5-amino-1,10-phenanthroline (APHEN), iminodiacetic acid (IDA), and iminodimethyl phosphonic acid (IDP). The performance of the resulting microreactors in Suzuki−Miyaura cross-coupling reactions was evaluated, finding that the poly(GMA-co-EDMA) monolith chemically modified with 5-amino-1,10-phenanthroline as a binding site for the palladium catalyst provided an excellent flow-through performance, enabling highly efficient and rapid reactions with high product yields. Moreover, this monolithic microreactor maintained its good activity and efficiency during prolonged use.

Carboxymethylcellulose-supported Palladium Nanoparticles Formed <i>in situ</i> for Suzuki-Miyaura Coupling Reaction

A green experiment is described here for direct fabrication of carboxymethylcellulose-supported palladium nanoparticles (PdNPs@CMC) in situ through a simple self-assemble and self-reduction process between carboxymethylcellulose (CMC-Na) and PdCl2 solution. The PdNPs@CMC was well characterized by ICP, UV-Vis, XPS, FTIR, SEM, and TEM techniques. The in situ synthesized PdNPs@CMC was proved to be an efficient catalyst for Suzuki-Miyaura coupling reaction under mild aerobic conditions. The superior catalytic performance of PdNPs@CMC is attributed to the coordination with carboxyl groups (−COO−) and free hydroxyl groups (−OH) as well as polymeric capping effect of CMC. Moreover, the catalyst showed no significant loss of its activity at least three consecutive cycles. This laboratory class is involved in the preparation and characterization of PdNPs@CMC as well as its catalytic application in Suzuki−Miyaura cross coupling reaction under green conditions. This laboratory class is suggested to divide into two parts. The first part includes the fabrication of catalyst in situ through a self-assemble and self-reduction of Pd(II) with CMC−Na, and characterization of the as-prepared catalyst using various techniques. The second part employs the resulting catalyst to perform a microscale Suzuki-Miyaura reaction, recycling of catalyst, and characterization of the product. By design, this comprehensive experiment set up for the third-year undergraduate, and aim to make students comprehend the concept of ion-exchange reaction, reduction reaction, carbon-carbon coupling reaction, supported catalysts, nanoparticles, and green chemistry as well as train the fundamental operation capability of students, and improve their experimental skills.

Synthesis of arenediazonium salts and Suzuki- Miyaura cross-coupling reaction in microreactors

The process characteristics of two main steps in the preparation of 4-nitrobiphenyl (4-NBP) from 4-nitroaniline (PNA) were clearly revealed by applying two continuous-flow microreactors. The first step was the synthesis of 4-nitrobenzene diazonium tetrafluoroborate (4-NBDT) through the diazotization reaction. The reaction temperature, the residence time, and the molar ratio of different reactants were investigated to achieve optimal reaction conditions with the highest yield of 4-NBDT. Notably, the yield of 4-NBDT reached 97% at 25 °C only in 2.3 s with the optimal molar ratio of HBF4, NaNO2 and PNA (i.e., 2.72:1.05:1). The second step was the Suzuki-Miyaura cross-coupling reaction, in which HNO3 was used to transform the reaction system into a homogeneous state. The effects of mixing performance, the molar percentage of Pd(OAc)2 to 4-NBDT, the reaction temperature and the residence time on the Suzuki-Miyaura cross-coupling reaction were investigated systematically. With the molar percentage of Pd(OAc)2 to 4-NBDT of 1 mol%, the yield of 4-nitrobiphenyl (4-NBP) was optimized to 99% in just 13 min at 25 °C. This study demonstrated the excellent potential of utilizing the continuous-flow microreactor for the diazotization and the following Suzuki-Miyaura cross-coupling reaction.

In situ investigation of hot-electron-induced Suzuki−Miyaura reaction by surface-enhanced Raman spectroscopy

The palladium-catalyzed Suzuki−Miyaura cross coupling reaction is one of the most useful methods for forming carbon—carbon bonds. In addition to traditional thermal activation, plasmonic photocatalysts can also promote this reaction under light illumination. However, it is still debated whether hot electron transfer or localized thermal heating is the main driving force of this reaction. Herein, we utilize in situ surface-enhanced Raman spectroscopy to characterize the Suzuki–Miyaura reaction on the surface of Au@Pd nanoparticles. We exclude the possibility that plasmon-induced heating drives the reaction, and we confirm the hot-electron mechanism by demonstrating a linear relationship between the reaction rate and laser power. Based on these results, we propose that the hot-electron transfer mechanism is the primary route for the plasmon-driven heterogeneous Suzuki−Miyaura cross coupling reaction. These results may help the rational design of photocatalysts.

Zeolite enslaved transition metal complexes as novel heterogeneous catalysts for synthesis of polycyclic heterocycles using suzuki--miyaura cross coupling reaction under greener conditions

In the present work we report the construction of zeolite enslaved transition metal complexes (Pd2+, Ni2 + ) as novel heterogenous catalysts for synthesis of polycyclic heterocycles using suzuki–miyaura cross coupling reaction in ethanolic medium. The synthesized catalysts were characterized by employing UV–Vis, FT-IR, magnetic susceptibility, N2 sorption, XRD, XPS, FE-SEM analysis. Results of the study advocate that newly developed catalysts give rise to a rapid and easy synthesis of various polycyclic heterocycles by Suzuki coupling reactions in impressive yields. In conclusion, developed catalyst may be used as versatile tool in the synthesis of various industrially and pharmaceutically important polycyclic heterocycles under greener conditions.

From Electronic Waste to Suzuki-Miyaura Cross-Coupling Reaction in Water: Direct Valuation of Recycled Palladium in Catalysis.

From electronic waste to Pd-catalyzed reaction! The straightforward valuation of palladium recovered from electronic waste is reported here. Following a classical leaching stage, palladium is selectively extracted from a complex aqueous mixture of metallic cations into an organic phase. Afterwards, the judicious choice of a surfactant enables stabilization of palladium during back extraction cycles, and the direct preparation of an aqueous micellar solution, which can be employed in a model Suzuki-Miyaura cross-coupling reaction. Clean phase separation is observed, and distribution of all components between organic and aqueous phases is mastered. The proposed process avoids several waste generating steps dedicated to palladium isolation and ultimate purification, as well as the preparation of palladium pre-catalyst. This novel approach enables a better use of both natural resources and industrial wastes, through new cycles in circular economy.

Robust NHC-palladacycles-catalyzed Suzuki−Miyaura cross-coupling of amides via C-N activation

Robust NHC-palladacycles (NHC = N-heterocyclic carbene) were synthesized and exhibited high catalytic activity towards Suzuki−Miyaura cross-coupling reactions between inactive amides with N-acetyl/benzyl substituents and aryl boronic acids, producing diverse ketones in good to excellent yields. This unprecedented and practical palladacycles-catalyzed Suzuki−Miyaura cross-coupling of amides with boronic acids via selective C-N bond activation was attributed to the strong σ-donor and weak π-acceptor properties of acenaphthoimidazolylidene, which may highlight their potential in other challenging coupling transformations involving inactive amides.

Palladium Nanoparticles Supported on Hydroxyapatite Nanospheres: Highly Active, Reusable and Green Catalyst for Suzuki – Miyaura Cross Coupling Reactions under Aerobic Conditions

AbstractThe development of simply prepared, highly active and reusable nanocatalysts for Suzuki‐Miyaura cross coupling reactions under mild and green conditions remains a challenge in the field of synthetic organic chemistry. Herein, we describe a new nanocatalyst comprising of palladium nanoparticles supported on hydroxyapatite nanospheres, which can reproducibly be formed in‐situ during the Suzuki‐Miyaura coupling reactions starting with Pd(II)‐exchanged nanohydroxyapatite. The characterization of the resulting catalyst by using ICP‐OES, P‐XRD, XPS, TEM, HRTEM, SEM and N2‐adsorption‐desorption analyses revealed that the formation of 3.7 ± 1.3 nm palladium(0) nanoparticles (Pd(0)∼430 nanoclusters) on the surface of nano‐sized (∼ 50 nm) hydroxyapatite (nano‐HAp) support by keeping the host framework intact. This previously unappreciated combination of Pd NPs and nano‐HAp (PdNPs@nano‐HAp) shows excellent activities (TOF's > 3×105 h−1) in the Suzuki–Miyaura cross coupling reactions of different arylbromides with phenylboronic acid under mild, green and aerobic conditions. More importanly, these new supported palladium(0) nanoparticles were found to be highly durable nanocatalyst throughout the reusability experiments, they maintain almost their inherent activity after 10th catalytic cycle at high conversion (> 98%).

Synthesis, properties and structure of borafluorene-based conjugated polymers with kinetically and thermodynamically stabilized tetracoordinated boron atoms

Herein, borafluorene-conjugated polymers with a dibromoborafluorene monomer and various boronic acid ester comonomers are reported. By employing the Suzuki−Miyaura cross-coupling reaction, a series of copolymers was prepared with the boron atoms in tetracoordinated states. Based on comparison to the optical properties of gallafluorene copolymers, higher luminescence quantum yields were obtained from the synthesized borafluorene copolymers due to the weak spin-orbit interaction of boron compared to that of gallium. Additionally, the results from the electrochemical measurements indicated that the electron-withdrawing property of the boron atoms led to stabilization of the lowest unoccupied molecular orbitals (LUMOs) of the borafluorene copolymers. In the X-ray diffraction profiles, significant peaks originating from π−π stacking and assembly of the side chains were observed. The borafluorene copolymers were more crystalline than the gallafluorene polymers. Synthesis and properties of borafluorene-containing conjugated polymers with various comonomers are presented. From the comparison with the gallafluorene copolymers, higher luminescent quantum yields were obtained from the borafluorene copolymers. Additionally, from the electrochemical measurements, it was shown that the electron-withdrawing property of the boron atoms led to the stabilization of LUMOs of the borafluorene copolymers. In the X-ray diffraction profiles, the significant peaks originated from π−π stacking and assembly of the side chains were observed. The borafluorene copolymers were more crystalline materials relative to the gallafluorene polymers.

Efficient Access to Original 6-Substituted 5-Nitro-2,3-dihydro­imidazo[2,1-b]oxazoles

A one-pot sequential intramolecular cyclization and Suzuki–Miyaura or Sonogashira reaction under microwave irradiation are reported in the 5-nitro-2,3-dihydroimidazo[2,1-b]oxazole series. The intramolecular cyclization of 1-(2,4-dibromo-5-nitro-1H-imidazol-1-yl)propan-2-ol between the hydroxyethyl group and the bromine atom at the 2-position is carried out first, followed by optimization and generalization of the Suzuki–Miyaura and Sonogashira cross-coupling reactions of the bromine atom at the 4-position. The various boronic acids and alkynyl derivatives used to perform these palladium-catalyzed cross-coupling reactions allowed to substitute the 6-position of 5-nitro-2,3-dihydroimidazo[2,1-b]oxazole compounds.

Bike peptides: a ride through the membrane.

Several natural peptides have a biaryl or biaryl ether motif in their biologically active structures. A model bicyclic pentapeptide containing a biaryl bridge has been synthesized by solid-phase peptide synthesis combining on-resin Suzuki and Miyaura cross-coupling reactions. Its biological properties in terms of permeability, stability and cytotoxicity have been studied, demonstrating the positive contribution of the biaryl bridge, excellent membrane penetration and serum stability Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

Palladium-Alumoxane Framework as a Novel and Reusable Nanocatalyst for Suzuki–Miyaura, Stille and Heck Cross Coupling Reactions

Herein for the first time, a Schiff base alumoxane-supported palladium (SBA-Pd°) were successfully synthesized and reported as a new mesoporous nanocatalyst for C–C cross coupling reactions. The SBA-Pd° nanocatalyst could be dispersed in poly(ethylene glycol) and showed excellent catalytic activity for Suzuki–Miyaura, Stille and Heck coupling reactions. In addition, the nanocatalyst could be recovered and reused several times without significant loss of its catalytic activity. Pd leaching from SBA-Pd° is very negligible for this coupling reaction.

Palladium catalysed sequential imine arylation/Suzuki–Miyaura coupling: synthesis of α-(biarylyl)benzylamines

We report an innovative, high yielding one-pot sequential catalytic imine arylation/Suzuki–Miyaura cross-coupling reaction, which converts suitably activated imine substrates to various biarylarylmethyl amine products using several commercial Pd catalysts. Many biarylarylmethyl amine molecules are biologically active. Insightful computational studies detail the mechanism of the imine arylation process. The sequence of reactions is likely to be dependent on the reaction conditions.

New Pd(II) and Pt(II)-diaminophosphine complexes bearing cyclohexyl or isopropyl moiety: use of Pd(II) complexes as precatalyst in Mizoroki--Heck and Suzuki--Miyaura cross-coupling reactions

Two new diaminophosphine ligands, $N$,$N$'-bis(dicyclohexylphosphino)-2-(aminomethyl)aniline (\textbf{1}) and $N$,$N$'-bis(diisopropylphosphino)-2-(aminomethyl)aniline (\textbf{2}) were synthesized by the reaction of 2-(aminomethyl)aniline with two equivalents of Cy$_{2}$PCl or (iPr)$_{2}$PCl, respectively. The reactions of \textbf{1 }and \textbf{2} with MCl$_{2}$(cod) (M = Pd, Pt; cod = 1,5-cyclooctadiene) yield complexes [\textit{cis}-Pd(L$_{2}$\textbf{P}NHC$_{6}$H$_{4}$CH$_{2}$NH\textbf{P}L$_{2})$Cl$_{2}$] (L = Cy \textbf{3}, iPr \textbf{4}) and [\textit{cis}-Pt(L$_{2}$\textbf{P}NHC$_{6}$H$_{4}$CH$_{2}$NH\textbf{P}L$_{2})$Cl$_{2}$] (L = Cy \textbf{5}, iPr \textbf{6}), respectively. The catalytic activity of the palladium complexes was investigated in the Suzuki--Miyaura cross-coupling reaction in the presence of Cs$_{2}$CO$_{3}$ as a base. The palladium complexes were also found to be highly active catalysts in the Mizoroki--Heck reaction.

Efficient C--C cross-coupling reactions by (isatin)-Schiff base functionalized magnetic nanoparticle-supported Cu(II) acetate as a magnetically recoverable catalyst

Copper catalysts were simply fabricated through surface modification of superparamagnetic iron nanoparticles with indoline-2,3-dione(isatin)-Schiff-base and interaction with Cu from low-cost commercially available starting materials. Catalysts were characterized using atomic absorption spectrophotometry, Fourier transform infrared spectroscopy, X-ray diffraction, thermogravimetric analysis, vibrating sample magnetometry, UV/Vis spectroscopy, scanning electron microscopy, and transmission electron microscopy. These catalysts showed high efficiency for phosphine-free Mizoroki--Heck and Suzuki--Miyaura cross-coupling reactions with good diversity and generality. The catalysts could be easily recovered and reused several times without a significant loss in their catalytic activity and stability.

Substituted 2-(2''-pyridyl)benzimidazole palladium(II) complexes as an efficient catalytic system for Suzuki--Miyaura cross-coupling reactions

A new series of $N,N$-type 2-(2'-pyridyl)benzimidazole ligands (\textbf{2A}$_{\mathbf{1}}$,\textbf{ 2A}$_{\mathbf{2}}$,\textbf{ 3B}$_{\mathbf{1}}$,\textbf{ 3B}$_{\mathbf{2}}$,\textbf{ 3B}$_{\mathbf{3}}$, and\textbf{ 4C}$_{\mathbf{1}})$ and their Pd(II) complexes (\textbf{5A}$_{\mathbf{1}}$,\textbf{ 5A}$_{\mathbf{2}}$,\textbf{ 6B}$_{\mathbf{1}}$,\textbf{ 6B}$_{\mathbf{2}}$,\textbf{ 6B}$_{\mathbf{3}}$, and\textbf{ 7C}$_{\mathbf{1}})$ were prepared and characterized by conventional spectroscopic methods and elemental analyses. The incorporation of $N$-coordinated benzimidazole complexes of palladium gave high catalytic activity in the Suzuki--Miyaura coupling of aryl halides substrates. After determining the best active catalyst as \textbf{5A}$_{\mathbf{1}}$, bearing the mesityl substituent on the benzimidazole ring with the Pd(II) ion, optimization studies were carried out via changing the substrate, base, time, atmosphere, and the effect of water. The DMF:H$_{2}$O (4/1) and Cs$_{2}$CO$_{3}$ as base were found to be critical for the efficiency of the reaction yield (100{\%}).

Resorcinarene-mono-benzimidazolium salts as NHC ligands for Suzuki--Miyaura cross-couplings catalysts

Two mono-benzimidazolium salts of resorcinarene have been prepared and used as ligands in Suzuki--Miyaura cross-coupling reactions. They have been fully characterized by $^{1}$H and $^{13}$C NMR, MALDI, and FT-IR spectroscopic methods, and their structures were confirmed by X-ray diffraction analysis. These two new resorcinarene-based mono-benzimidazolium salts showed good catalytic activity for coupling reactions in DMF. The highest conversion was achieved for arylation of 4-bromotoluene using the resorcinarenyl mono-dimethylbenzimidazolium salt.

Monodisperse palladium nanoparticles supported on chemically derived graphene: highly active and reusable nanocatalysts for Suzuki--Miyaura cross-coupling reactions

Addressed herein is the catalysis of monodisperse palladium nanoparticles (NPs) supported on chemically derived graphene (CDG) for the Suzuki--Miyaura cross-coupling of phenylboronic acid and various aryl halides. Monodisperse Pd NPs were synthesized by the solution phase reduction of palladium(II) acetylacetonate with morpholine borane complex in oleylamine and deposited on CDG via the liquid phase self-assembly method. Colloidal Pd NPs and CDG-Pd catalyst were characterized by TEM, XRD, SEM, and ICP-MS analyses. The CDG-Pd catalyst showed high activity in the Suzuki--Miyaura cross-couplings of different aryl halides including iodides, bromides, and even chlorides with phenylboronic acid under mild conditions. More importantly, the reusability experiments revealed that CDG-Pd catalyst was highly durable by almost maintaining its inherent activity after the 15th catalytic cycle.

One-Pot Chemoselective Synthesis of 2,4,6,8-Tetrasubstituted Quinazolines via Microwave-Assisted Consecutive Bis-SNAr/Bis-Suzuki–Miyaura Cross-Coupling Reactions

A practical and efficient synthesis of 2,4,6,8-tetrasubstituted quinazolines through one-pot chemoselective sequential bis-S_NAr/bis-Suzuki–Miyaura reactions under microwave irradiation is presented. The bis-S_NAr reaction occurs selectively at the C-2 and C-4 positions of 6,8-dibromo-2,4-dichloroquinazoline and the bis-Suzuki–Miyaura cross-coupling at C-6 and C-8. This procedure affords convergent synthesis of polysubstituted quinazoline derivatives in high yields in very few steps and tolerates a wide range of boronic acids and amines.